Since the May 2015 approval of HarnoviTM (sofosbuvir 400mg & ledipasvir 90mg), the first genotype-specific direct-acting antiviral (DAA) in chronic hepatitis C (HCV), there has been a rapid evolution of new DAAs to pangenotypic regimes, with high efficacy of sustained virological response (SVR) of >95 %. Non-responders to previous treatment, including DAA failures, can be successfully treated. Strategies to encourage community prescribing have made it possible to achieve total HCV elimination in Australia by 2026.

By Dr Wendy Cheng, Head Liver Service, RPH, Adjunct Prof, ECU.

Challenges still exist in the management of HCV including:

Assessment of fibrosis

Establishing cirrhosis is critical prior to treatment as surveillance for hepatocellular carcinoma (HCC) is required for cirrhotic patients even after SVR. As liver biopsy is not mandatory for treatment of HCV, non-invasive methods of fibrosis are currently being used. Accessibility to Hepascore, Fibroscan or Elastography may be limited in the community. APRI (AST platelet ratio index), a relatively simple test may be helpful to establish the presence of cirrhosis (i.e. APRI > 1). See www.hepatitisc.uw.edu/page/clinical-calculators/apri for more information.

Choice of DAA regimes

With the approval of pangenotypic drugs – EpclusaTM (sofosbuvir 400mg + velpatasvir 100mg) and MaviretTM (glecaprevir 100mg + pibrentasvir 40mg) in 2018, treatment of HCV is no longer restricted to genotype 1, 3 and 4. Patients with genotype 1 who do not have cirrhosis are eligible for 8 weeks’ of treatment with MaviretTM and those with viral load of < 6 X 10^6 IU/ml also for 8 weeks’ of HarvoniTM with SVR comparable to 12 week regimes. All DAA regimes are approved only for compensated cirrhosis. MaviretTM is also approved for specific DAA failures.

Patients with significant co-morbidities e.g. renal failure, coinfections with HBV or HIV and cirrhosis should be referred. Patients with decompensated liver disease may be transplanted before treatment of HCV, to reduce the risk of further decompensation.

Drug-drug interactions

Direct acting antiviral drugs have potentially serious drug-drug interactions with several commonly prescribed and over-the-counter medications. It is essential that prescribers refer to Liverpool DDI website prior to initiation of therapy (see www.hep-druginteractions.org).

Drugs include:

Proton pump inhibitors (PPI)

Statins

Antiepileptic medications – e.g. Phenytoin

Antiarrhythmic drugs – e.g. amiodarone

Antiretroviral drugs

Oral contraceptive pills – co-administration of MaviretTM with ethinyloestradiol-containing products is contraindicated due to the risk of ALT elevations

Consider stopping PPI as these may interfere with absorption of DAA with reduced SVR. If essential, low dose PPI once daily may be given at the same time as DAAs, and with EpclusaTM 4 hours before or after PPI.

Statins have variable interactions with DAA, some with absolute contraindications. Phenytoin is contraindicated in all DAA regimes and alternative antiepileptic drugs found. Amiodarone has been associated with severe bradycardia with DAA.

Patients should be advised to check with the prescriber with all medications whilst on treatment.

Patients with HBV-HCV coinfection should have HBV treated at the same time. Those with past HBV infection should have ALT monitored and if it rises HBV DNA should be performed to check for HBV reactivation (uncommon and treatable). There is little evidence to indicate increased risk of HCC with DAA treatment, however, those with HCC should have it treated before DAA treatment is commenced.

Treatment of HCV in primary care

Online learning modules are available for GPs to get involved in the treatment of HCV – as independent accredited prescribers, referral to tertiary centres, or screening of high-risk patients – depending on training and expertise.

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